Prospective review of biomarkers and revascularization in 2251 patients with chronic coronary syndrome over 12.6 years

Background The role of cardiovascular biomarkers in detecting coronary obstruction and predicting outcomes after revascularisation in chronic coronary syndrome (CCS) remains unclear. Methods Patients undergoing coronary angiography for suspected CCS were prospectively studied (n=2,251; median follow up 12.6 years). Obstructive coronary artery disease (CAD) was defined as at least 50% stenosis in at least 1 major epicardial vessel. High sensitivity cardiac troponin T (hsTnT), N terminal pro B type natriuretic peptide (NTproBNP), high sensitivity C reactive protein (hsCRP), interleukin6 (IL6), and copeptin were measured. Diagnostic performance was assessed by receiver operating characteristic (ROC); survival analysis used multivariate Cox regression with biomarker vs. treatment interaction testing. Results Overall 888 patients (39.4%) had obstructive CAD. Only hsTnT provided meaningful diagnostic capacity (area under the curve [AUC] 0.669), comparable to risk factor weighted clinical likelihood (RF CL; AUC 0.663), with incremental dignostic benefit inversely proportional to RF CL category (delta AUC: very low 10.4%, low 8.0%, intermediate/high 5.0%). NT-proBNP was the strongest universal mortality predictor across optimal medical therapy (OMT; (hazard ratio [HR] (1.488, 95%CI 1.288;1.720, p<0.001), percutaneous coronary intervention (PCI; HR 1.220, 95%CI 1.020;1.458, p=0.029), and coronary artery bypass grafting (CABG; HR 1.220, 95%CI 1.049;1.420, p=0.010). Interaction analysis validated a data-derived 150 pg/mL threshold (p=0.032): below it, mortality was comparably low irrespective of revascularisation status (HR 0.98, 95%CI 0.67;1.43, p=0.910); above it, baseline mortality risk was markedly elevated (HR 5.75, 95%CI 4.10;8.00, p<0.001) and revascularisation associated with 40% mortality reduction, though substantial residual risk persisted (HR 3.43, 95%CI 2.70;4.40, p<0.001). Conclusions HsTnT provides meaningful diagnostic value with RF CL category-specific incremental benefit. NT-proBNP emerged as a universal prognostic marker identifying patients with distinct revascularisation associated mortality reduction driven by differential baseline risk.